The enteric nervous system (ENS) has been found to contain intrinsic serotonergic neurons. We hope to exploit the superior accessibility of the ENS to study the cellular biology of these neurons. In addition, we will try to define the relationship of enteric serotonergic neurons to other identified neuronal elements of the ENS, such as peptidergic neurons and adrenergic neurites. Finally, we hope to enhance understanding of the ENS itself by morphologically examining the relationships of its component neurons to each other, the nature of enteric ganglia, and intrinsic enteric pathways. Properties of enteric serotonergic neurons to be examined will include: (1) uptake of the precursor amino acid, L-tryptophan; (2) regulation of the uptake of serotonin (5-HT); (3) vesicles and the binding protein that may be involved in the subcellular storage of 5-HT; (4) factors involved in regulating 5-HT release; (5) characterization of enteric 5-HT receptors. Enteric neurons will also be studied morphologically, cytochemically, immunocytochemically and by radioautography. Two or more neurons will be simultaneously identified by combining these techniques. Neurons that behave physiologically as if they receive a serontonergic innervation, tonic type neurons, will be identified and marked. The serotonergic input to these identified cells will then be examined along with the tonic type neurons by electron microscopic radioautography.